Proteases and their Receptors as Mediators of Inflammation-Associated Colon Cancer

Author(s): Elizabeth H. Trusevych, Wallace K. MacNaughton.

Journal Name: Current Pharmaceutical Design

Volume 21 , Issue 21 , 2015

Abstract:

Chronic inflammation increases the risk of developing cancer. For example, patients with severe and prolonged inflammatory bowel disease, particularly ulcerative colitis, have a significantly higher risk of developing colorectal cancer. Serine proteases coordinating the coagulation cascade and immune cell proteases play important roles in regulating the inflammatory response through their actions on protease-activated receptors (PAR). PARs and their activating proteases have also been implicated in many cancers, including CRC. Importantly, the actions of proteases could be important for mediating the transition from chronic inflammation to cancer. PAR activation has been shown to have pro-tumourigenic effects including the production of matrix metalloproteinases that can promote tumour cell growth and metastasis, and transactivation of the epidermal growth factor receptor, which is a main target for cancer treatment. Additionally, PAR activation can also result in increased expression of cyclooxygenase (COX)-2, an important enzyme mediating inflammation, resolution, and cancer progression. In this review, we will highlight our current knowledge about the effects of proteases and their receptors on intestinal inflammation and cancer, and explore the potential role of PAR-induced COX-2 on colitis-associated cancer.

Keywords: colitis-associated cancer, colorectal cancer, cyclooxygenase-2, inflammatory bowel disease, protease-activated receptors, serine proteases.

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Article Details

VOLUME: 21
ISSUE: 21
Year: 2015
Page: [2983 - 2992]
Pages: 10
DOI: 10.2174/1381612821666150514104800
Price: $58

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